GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord.
GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord.
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DOI：
10.1038/srep04094
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发表时间：
2014-02-13
影响因子：
4.6
通讯作者：
Salter MW
中科院分区：
文献类型：
--
作者：
Hildebrand ME;Pitcher GM;Harding EK;Li H;Beggs S;Salter MW
突触后离子受体接受突触前释放的递质，其组成不仅对电信号的传导和整合至关重要，而且对协调下游生化信号通路至关重要。在成人中枢神经系统的谷氨酸能突触中，大量证据表明突触反应的NMDA受体（NMDAR）成分由含有GluN2A亚基的NMDAR主导，而含有GluN2B、GluN2C或GluN2D的NMDAR在突触传递中起次要作用。在这里，我们发现nmdar介导的突触反应具有成人中枢神经系统中其他地方未描述的特征。我们发现含有glun2a的受体对突触NMDAR反应贡献不大，而GluN2B在成人脊髓I层神经元突触中占主导地位。此外，我们提供了glun2d介导的突触NMDAR成分在成人I层神经元中的证据。引人注目的是，GluN2D介导的电荷转移远远超过GluN2A，与GluN2B相当。第一层形成了一条独特的从脊柱疼痛处理网络到大脑疼痛网络的输出通路。我们在第一层神经元中发现的glun2d介导的突触反应为缓慢、持久和前馈放大提供了分子基础，这是疼痛的基本特征。
The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also for coordinating downstream biochemical signaling pathways. At glutamatergic synapses in the adult CNS an overwhelming body of evidence indicates that the NMDA receptor (NMDAR) component of synaptic responses is dominated by NMDARs containing the GluN2A subunit, while NMDARs containing GluN2B, GluN2C, or GluN2D play minor roles in synaptic transmission. Here, we discovered NMDAR-mediated synaptic responses with characteristics not described elsewhere in the adult CNS. We found that GluN2A-containing receptors contribute little to synaptic NMDAR responses while GluN2B dominates at synapses of lamina I neurons in the adult spinal cord. In addition, we provide evidence for a GluN2D-mediated synaptic NMDAR component in adult lamina I neurons. Strikingly, the charge transfer mediated by GluN2D far exceeds that of GluN2A and is comparable to that of GluN2B. Lamina I forms a distinct output pathway from the spinal pain processing network to the pain networks in the brain. The GluN2D-mediated synaptic responses we have discovered in lamina I neurons provide the molecular underpinning for slow, prolonged and feedforward amplification that is a fundamental characteristic of pain.
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影响因子：
16.2
作者：
Hatton, CJ;Paoletti, P
通讯作者：
Paoletti, P
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作者：
LIMA, D;COIMBRA, A
通讯作者：
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